Search

Summary Assessment tools must be investigated for reliability, validity and feasibility before being implemented. In 2013, the Australian and New Zealand College of Anaesthetists introduced workplace-based assessments, including a direct observation of a procedural skills assessment tool. The objective of this study was to evaluate the psychometric properties of this assessment tool for ultrasound-guided regional anaesthesia. Six experts assessed 30 video-recorded trainee performances of ultrasound-guided regional anaesthesia. Inter-rater reliability, assessed using absolute agreement intraclass correlation coefficients, varied from 0.10 to 0.49 for the nine individual nine-point scale items, and was 0.25 for a ‘total score’ of all items. Internal consistency was measured by correlation between ‘total score’ and ‘overall performance’ scale item (r = 0.68, p

OBJECTIVE The best dynamic test for the assessment of the hypothalamic–pituitary–adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic–pituitary–adrenal axis. DESIGN Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed. SETTING Programmed Investigation Unit. SUBJECTS Fifty-seven healthy volunteers and 166 patients. MAIN OUTCOME MEASURES Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycaemia (plasma glucose 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission. CONCLUSIONS Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

In this study we examined the effects of insulin on protein kinase C (PKC) activity in cultured fetal chick neurons. PKC activity, measured as 32P incorporation into histone H1 in the presence of calcium (500 microM), phosphatidylserine (100 micrograms/ml), and diolein (3.3 micrograms/ml) minus the incorporation in the presence of calcium alone, was detected in neuronal cytosolic (207 +/- 33 pmol/min/mg) and membrane (33 +/- 8 pmol/min/mg) fractions. Insulin added to intact neurons increased the activity of PKC in both cytosolic and membrane fractions by about 40%. Neurons preincubated with cycloheximide (10 micrograms/ml) 30 min prior to insulin treatment showed the same degree of stimulation of PKC activity by insulin. The activation of PKC was maximal within 5-10 min of insulin exposure and was sustained for at least 60 min. Insulin stimulated PKC in a dose-dependent manner, with a maximal response obtained at 100 ng/ml. Addition of phosphatidylserine and diolein to neuronal cell extracts resulted in the phosphorylation of four major cytosolic proteins (70, 57, 18, and 16 kDa) and one major membrane protein (75 kDa). Phosphorylation of all five proteins was increased 2-fold in extracts from insulin-treated neurons. Immunoblot analysis of whole cell extracts using antibodies against PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon revealed that cultured fetal chick neurons contained only one of these PKC isoforms, the epsilon-isoform. The enzyme was mostly cytosolic. Insulin had no effect on either the amount of distribution of PKC-epsilon in cultured neurons but induced a small change in the mobility of PKC-epsilon on sodium dodecyl sulfate-polyacrylamide gels. When assay conditions were designed to measure specifically the activity of PKC-epsilon, using a synthetic peptide substrate in the absence of calcium, activity was 50 +/- 12% higher in insulin-treated cells (p less than 0.005). PKC activity in control and insulin treated-neurons was almost completely inhibited when assays included a peptide identical to the pseudo-substrate binding site of PKC-epsilon. We conclude that PKC-epsilon is the major PKC isoform present in cultured fetal chick neurons. Insulin stimulates PKC-epsilon activity by a mechanism that does not involve translocation of the enzyme from cytosol to membrane.

Using neutron diffraction and a specially constructed high pressure cell suitable for aligned multibilayer systems, we have studied, as a function of pressure, the much observed anomalous swelling regime in dimyristoyl- and dilauroyl-phosphatidylcholine bilayers, DMPC and DLPC, respectively. We have also reanalyzed data from a number of previously published experiments and have arrived at the following conclusions. (a). The power law behavior describing anomalous swelling is preserved in all PC bilayers up to a hydrostatic pressure of 240 MPa. (b). As a function of increasing pressure there is a concomitant decrease in the anomalous swelling of DMPC bilayers. (c). For PC lipids with hydrocarbon chainsor=13 carbons the theoretical unbinding transition temperature T small star, filled is coupled to the main gel-to-liquid crystalline transition temperature T(M). (d). DLPC is intrinsically different from the other lipids studied in that its T small star, filled is not coupled to T(M). (e). For DLPC bilayers we predict a hydrostatic pressure (290 MPa) where unbinding may occur.

The hormonal and metabolic effects of the somatostatin analogue SMS 201-995 have been examined in normal and diabetic humans. When 50 micrograms of analogue was administered subcutaneously at 8 A.M. and 5:30 P.M., growth hormone secretion over 24 hours was not significantly affected, and the nocturnal growth hormone surge persisted in normal subjects and in type II diabetic patients. Insulin secretion was suppressed in both groups, but glucose tolerance deteriorated only in the normal subjects. Gastrointestinal side effects developed in both groups. Subcutaneous administration of 50 micrograms of SMS 201-995 at 11 P.M. decreased nocturnal growth hormone secretion (peak, 5 +/- 2 milliunits/liter versus 23 +/- 6 milliunits/liter; p less than 0.01) in normal subjects. Postprandial circulating glucose and insulin levels the following day were unaffected by SMS 201-995, and no side effects were observed. In type I diabetic patients receiving a variable rate insulin infusion overnight to maintain normoglycemia, SMS 201-995 (50 micrograms) administered at 11 P.M. decreased insulin requirements for two to three hours after injection. Insulin sensitivity thereafter was unaffected despite suppression of growth hormone secretion. Alternative dosage regimens are necessary to suppress growth hormone release over 24 hours and to minimize side effects in type II diabetes. Administration of the analogue in the late evening suppresses growth hormone secretion overnight, but the "dawn phenomenon" persists in type I diabetic patients.

Changes in thyroid hormone concentration and distribution and plasma cortisol levels have been followed in 11 patients undergoing elective cholocystectomy. A significant rise in total and free thyroxine (T4) and fall in total and free triiodothyronine (T3) were noted after surgery. Reverse T3 concentrations rose substantially, suggesting that peripheral conversion of T4 to T3 is diminished and that there is preferential formation of reverse T3. Serum thyroid stimulating hormone concentrations did not change. There was no direct correlation between the change in cortisol and the change in thyroid hormone or reverse T3 concentrations.

Eight patients who had received megavoltage therapy for Cushing's disease 5-12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic-pituitary function. One patient showed clear evidence of relapse of Cushing's disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary-adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic-pituitary function follow mega-voltage therapy and these may progress to overt hypopituitarism.

Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1.5 to 8.5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone greater than 20 nmol/l) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean +/- SEM prolactin, 288 +/- 36 mU/l, patients, n = 7; 291 +/- 21 mU/l, controls, n = 9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin-releasing hormone, 200 micrograms (at 20 min, 2417 +/- 658 mU/l, patients, n = 7; 2113 +/- 424 mU/l, controls, n = 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 +/- 536 mU/l, patients, n = 7; 5858 +/- 460 mU/l, controls, n = 8) and insulin-induced hypoglycaemia (at 60 min, 1441 +/- 551 mU/l, patients, n = 7; 1298 +/- 183 mU/l, controls, n = 7) were similar in patients and controls. Two different radioimmunoassays using two different antisera gave similar estimates of serum prolactin levels and prolactin bioactivity in serum was normal in an in-vitro bioassay based on the ability of prolactin to stimulate proliferation of Nb2 node rat lymphoma cells (basal bioassayable prolactin, patients 355 +/- 43 mU/l, n = 10; controls 348 +/- 64 mU/l, n = 7). Metabolic abnormalities similar to those previously noted in hyperprolactinaemia were observed in the patients' 24 h profiles. These included mild hyperglycaemia (24 h mean +/- SEM glucose, 5.47 +/- 0.08 mmol/l, patients; 5.05 +/- 0.14 mmol/l, controls; P less than 0.05) and elevations in circulating lactate, pyruvate and alanine. Blood glycerol was decreased (24 h mean +/- SEM, 0.044 +/- 0.004 versus 0.058 +/- 0.004 mmol/l, P less than 0.05). In the majority of patients with idiopathic galactorrhoea, prolactin concentrations, regulation of secretion and bioactivity in vitro are normal. The galactorrhoea and metabolic abnormalities suggest increased tissue sensitivity to the lactogenic and metabolic actions of prolactin, while ovarian cyclical function is relatively spared.

An alteration of the hypothalamic dopaminergic regulation of LH secretion has been implicated in the abnormal LH secretion of polycystic ovarian syndrome (PCOS). To investigate this, the acute effect of dopamine (DA) receptor blockade on LH, FSH, PRL and TSH secretion was determined. No effect was observed on either LH or FSH secretion in the PCOS patients or in normal women and LH pulsatility appeared to be maintained. When the PCOS patients were divided into those who ovulated in the preceding cycle and those who were anovulatory, it was observed that the ovulatory patients had a normal PRL and TSH response; whereas in the anovulatory patients, the PRL rise was blunted and the TSH response was absent. We conclude that this study gives no evidence to support the hypothesis of altered hypothalamic DA regulation of LH secretion in PCOS. The lack of LH response to DA blockade suggests that a physiological role of DA in the control of LH secretion seems unlikely as determined under these experimental conditions. The differences in PRL and TRH response may reflect anovulation rather than a fundamental abnormality in PCOS.

Ten endocrinologically normal men with secondary sexual impotence were given 500 microng LHRH subcutaneously every 8 h. After 4 weeks treatment the LH response to 500 microng LHRH was reduced from a peak of 35.7+/-5.2 to 16.8+/-3.5 mu/ml (P less than 0.01) and the FSH response from 4.2+/-0.93 to 2.39+/-0.4 mu/ml (P greater than 0.01). Circulating total testosterone, oestradiol, prolactin and sex hormone binding globulin showed no significant changes. Whether this inability of the pituitary to maintain it s response to LHRH is peculiar to impotent men requires further study.

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

The role of serotonin in the prolactin, growth hormone, ACTH and cortisol responses to hypoglycaemia has been investigated in normal subjects using a selective serotonin (5HT2) receptor antagonist, ketanserin. Circulating concentrations of these hormones were measured after administration of insulin (0.1 units/kg body weight iv) to eight normal male subjects with and without simultaneous iv ketanserin (10 mg). Plasma glucose fell to less than 2.0 mmol/1 in all subjects and was unaffected by ketanserin. Ketanserin induced a 50% decrease in the serum prolactin response to hypoglycaemia, 45 and 60 min after administration of insulin (increase in serum prolactin at 60 min: 1145 +/- 295 mU/l without ketanserin; 558 +/- 176 mU/l with ketanserin, P less than 0.05). The peak ACTH response was reduced by 30% (95.3 +/- 33.6 ng/l without ketanserin; 60.0 +/- 22.9 ng/l with ketanserin, P less than 0.05) but the plasma cortisol response was not significantly altered. The serum growth hormone response was unaffected by serotonin blockade. These findings suggest that serotonin, probably acting through 5HT2 receptors, is involved in the stimulation of prolactin and ACTH release but not in the release of growth hormone, during insulin induced hypoglycaemia.

The clinical, radiological, and biochemical effects of dopamine agonist withdrawal after long-term treatment were investigated in seven women and eight men who had been treated for prolactinomas for 1.5 to 7 (mean 3.7) years. Before treatment, serum prolactin concentrations were 1473 to 115 000 mU/l, all patients had abnormal radiological findings, and six had suprasellar extensions of pituitary tumours. Treatment with either bromocriptine or pergolide relieved symptoms and suppressed prolactin secretion in most patients. The size of the residual tumour was defined by doing fourth generation computerised tomographic scans immediately before termination of therapy, and evidence of tumour re-expansion was sought on scans repeated 5-39 weeks later. After discontinuation of treatment, symptoms recurred in 13 of 15 patients and hyper-prolactinaemia redeveloped in 14. Other pituitary function tests remained unchanged or improved. In 13 of 15 patients tumour or gland size did not change after withdrawal of treatment. One man had a marginal increase in tumour size, while in another the pituitary tumour shrank. Thus, although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

Cortisol, prolactin, and growth hormone responses to insulin-induced hypoglycemia were measured in 20 patients undergoing continuous ambulatory peritoneal dialysis or intermittent hemodialysis. The plasma cortisol responses were normal; however, the increments in serum prolactin and growth hormone concentrations were impaired in most patients. The growth hormone responses were lower (p less than 0.05) in those patients treated by continuous ambulatory peritoneal dialysis, but there were no other significant differences between the two patient groups. These results show that anterior pituitary dysfunction persists in some patients with chronic renal failure despite maintenance dialysis therapy.

Patients with hyperprolactinemia may be managed by pituitary surgery or irradiation, bromocriptine treatment, or a combination of these methods, and some patients remain untreated. Little is known of the long-term consequences of some of these therapeutic regimens. Forty-six hyperprolactinemic patients (40 female and six male) managed solely with bromocriptine or no treatment over a period of 12 months to six years were therefore evaluated in this study. Nine patients with radiologically normal pituitary fossae were untreated and 10 received bromocriptine, 7.5 to 10 mg daily, while 20 patients with radiologic evidence of a pituitary tumor were treated with bromocriptine, generally 10 to 20 mg daily. Patients were assessed clinically, biochemically, and radiologically before treatment and at least six weeks after discontinuation of therapy. A further seven patients were similarly assessed before and after eight bromocriptine-induced pregnancies. Symptoms persisted in the untreated group of nine patients, although menstruation returned in four of the females with previous amenorrhea; serum prolactin levels remained elevated, other pituitary function did not change, and pituitary fossae remained normal radiologically. In all patients treated with bromocriptine, symptoms improved irrespective of radiologic findings on the pituitary, and were abolished in 67 percent during treatment associated with a decrease in serum prolactin levels in all, and a return of levels to within normal limits in 80 percent of patients. Persistent side effects were usually dose-related, but remained troublesome in 13 percent. Bromocriptine-induced tumor regression was evident radiologically in all patients with suprasellar tumor tissue and in some with purely intrasellar adenomas. This effect occurred rapidly and persisted or increased throughout follow-up. On discontinuation of treatment, prolactin levels remained significantly lower than before therapy (mean 2,934 versus 5,052 mU/liter, p less than 0.05) but were within the normal range in only two patients. Other pituitary function was unaltered, or improved in some patients with definite tumors. Bromocriptine-induced pregnancy produced no permanent change in clinical, biochemical, or radiologic status. Long-term bromocriptine treatment for hyperprolactinemia is thus highly effective in alleviating symptoms and suppressing prolactin secretion, and induces persistent tumor regression on treatment without deterioration of other pituitary function in patients with macroadenomas. On discontinuation of therapy, however, hyperprolactinemia usually recurs, and treatment may therefore need to be continued for years.

10 men suffering with secondary sexual impotence were treated with luteinizing hormone-releasing hormone (LH-RH) in order to determine its effect on behavior. The patients were randomly and blindly allocated to start treatment with sc LH-RH 500 mcg every 8 hours or with a placebo injection. There were 2 treatment periods of 4 weeks separated by 2 weeks. Progress was assessed by a self-rating scale. Plasma testosterone LH follicle stimulating hormone plasma sex hormone binding globulin (SHBG) prolactin and urinary estrogens were measured. Patients found it difficult to distinguish between the placebo and treatment periods. Statistical analysis of the rating scale of interest in sex success in ejaculation frequency of intercourse occurrence of spontaneous erections and frequency of masturbation showed a significant improvement (p less than .05) during treatment with LH-RH. While an increase in spontaneous erection taken along showed significance evidence that LH-RH significantly improved the quality of erection or altered mood was absent.

Tyrosine hydroxylase activity was determined in eight brain regions: cerebral cortex, tuberculum olfactorium, nucleus accumbens, hypothalamus, amygdala, striatum, pons and medulla. Tyrosine hydroxylase activity was measured by the radiometric method of Hendry & Iversen (1971). After 30 days of chronic treatment, the specific activity of tyrosine hydroxylase was decreased t o a value below the sensitivity of the assay in all eight brain regions analysed. Within 36 h after withdrawing treatment, the activity of this enzyme had returned to control values in three brain regions, but was still significantly below control in another four (Fig. 1). Only the activity in the cerebral cortex remained undetectable, but this could be misleading, since control enzyme activity in this region was only 3 % of the striatal activity, and in control samples of cortex radioactivity was only twice blank values. The results of Fig. I suggest that the regions with the highest control activity recover more rapidly on withdrawal of the drug. Our results on the changes in tyrosine hydroxylase activity have been compared with catecholamine concentrations in the same regions. The results indicate that there appears to be no significant cell loss in the striatum, amygdala and nucleus accumbens after chronically treating rats with methamphetamine on the aforementioned drug regime. However, a direct comparison with the observations of Seiden e t a / . (1976) has not been made, since there may be species differences between rat and monkey, and until it has been determined whether the activity of tyrosine hydroxylase returns to control values in all regions after a longer period of withdrawal.

Osmoregulation of vasopressin secretion was studied in eight healthy women in the follicular and luteal phases of the menstrual cycle. Basal plasma osmolality in the luteal phase was significantly lower than in the follicular period (282.4 +/- 0.6, 285.6 +/- 1.1mmol/kg, respectively, P less than 0.05). Plasma AVP (pAVP) and plasma osmolality (pOsm) were measured during the infusion of 850 mmol/l saline in both phases of the cycle, and linear regression analyses of these data gave the following regression equations (i) follicular, pAVP = 0.43 (pOsm - 284), r = + 0.93, (ii) luteal, pAVP = 0.31 (pOsm - 279), r = + 0.95. Both the slope and abscissal intercept were significantly different (P less than 0.01). Osmotic threshold for thirst sensation in the luteal phase was lower than the follicular (293 +/- 2,297 +/- 1 mmol/kg, P less than 0.005). We conclude that, in the luteal phase, the threshold for AVP release and the gain or sensitivity of the osmostat are reduced together with lowering of the thirst threshold, which account for the lower basal luteal plasma osmolality.

Results of blood pressures (BP) and urinary electrolyte excretion studies are reported among several groups of adolescent and young adult females, both black and white, who were initially examined in high school and restudied at home 3--4 years later. Pooling of the data from the several cross-sectional studies (n = 662) revealed a weak but statistically significant positive correlation systolic blood pressure (SBP) and the urinary sodium (Na) excretion rate. Three of four correlations between SBP and potassium (K) were of an inverse nature. Although not statistically significant in their own right, when coupled with the Na/K excretion ratio, which was significantly associated with SBP, a moderating role for K is suggested. The urinary Na, K, and creatinine (Cr) excretion rates were highly intercorrelated and were correlated with weight. As measured by R2 in a stepwise regression analysis, weight contributed approximately 3% to the BP variance, and the urinary electrolytes accounted for approximately 2% of the SBP variance. Statistically significant partial correlation coefficients between SBP and Na, and Na/K, remained after adjusting for body weight.

The investigation is described of a 62-year-old female patient who presented with severe virilisation; her plasma testosterone concentration was grossly elevated at 37–9 nmol/L. Measurement of plasma androstenedione, dehydroepiandrosterone (DHEA) and DHEA-sulphate, urinary 17-oxosteroids and urinary ‘free’ Cortisol suggested an ovarian source of androgens. An ultrasound scan indicated the presence of an ovarian mass which was removed and classified as a Sertoli—Leydig cell tumour (arrhenoblastoma) combined with a mucinous cystadenoma. Following operation plasma testosterone levels returned to normal. The excessive pre-operative testosterone production appeared to have had little effect on the plasma level of SHBG, since levels remained similar before and after removal of the tumour. Serum LH and FSH levels were higher post-operatively.

The 24-h hormonal and metabolic profiles obtained in five non-insulin-dependent diabetics receiving twice daily s.c. injections of the long-acting somatostatin analogue SMS 201-995 (50 micrograms) have been compared with those obtained following placebo injection. Injections were given 30 min before breakfast and the evening meal. GH secretion was not suppressed by the analogue administered in this manner. Despite suppression of serum insulin levels following breakfast and the evening meal, blood glucose levels were similar during the two study periods with no evidence of worsening in diabetic control. Prolonged suppression of plasma glucagon levels was observed and the nocturnal elevation in serum TSH levels was abolished. Free T4 levels fell significantly following the analogue but total T3 levels were unaffected. Blood alanine levels were elevated throughout the study period following SMS 201-995 but changes in lactate, pyruvate, glycerol and 3-hydroxybutyrate were minor. All five subjects suffered gastrointestinal side-effects. SMS 201-995 (50 micrograms) given twice daily before meals does not cause a deterioration in metabolic control, does not suppress 24-h GH secretion and causes significant side-effects in patients with non-insulin-dependent diabetes mellitus.

SUMMARY We have studied the dose-response characteristics of the LHRH analogue D-Ser (TBU)6-Des Gly10-LHRH-ethylamide administered subcutaneously to five normal male volunteers. The relative potency of the analogue is about sixty times (FSH) and forty times (LH) that of the parent peptide and the increased potency and duration of action of the analogue lead to enhanced biological effect in terms of testosterone release. The prolonged duration of action of the analogue suggests that a single daily dosage regime could be used although further chronic studies with this potent analogue should be undertaken in normal volunteers to determine optimum dosage schedules.

Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.

The growth hormone (GH) response to iv injection of GH releasing hormone 1-44 (GHRH 1-44) has been examined in 10 hyperthyroid and 6 hypothyroid patients. Both groups of patients were studied at presentation and when euthyroid (mean 5 months for hyperthyroid, 8 months for hypothyroid). Hyperthyroid subjects demonstrated a peak mean (+/- SE) level of 17.7 +/- 3.8 mU/l, with an integrated GH 29.3 +/- 6.4 mU/l.h. When euthyroid the peak mean level was 17.0 +/- 5.0 mU/l and the integrated GH 22.8 +/- 4.2 mU/l.h. Neither change was statistically significant. Hypothyroid subjects had a peak mean level of 5.0 +/- 2.7 mU/l and integrated GH of 5.9 +/- 1.7 mU/l.h and when euthyroid a peak mean level of 7.1 +/- 4.8 mU/l and integrated GH of 8.1 +/- 3.6 mU/l.h. Body weight did not change significantly in this group of hypothyroid subjects with prolonged treatment. The increase in GH response to GHRH previously reported following replacement therapy may reflect a treatment-induced decrease in body weight, or may be a short term effect.

A boy aged two years presenting with advanced development of the genitalia, but with prepubertal testes, and accelerated growth is described. Investigation indicated pseudo-precocious puberty, due to idiopathic interstitial cell hyperplasia. Difficulties in interpretation of the hormonal studies were encountered due to an aberrant left testicular vein. This rare condition which has been called Testotoxicosis is probably due to an inborn error of metabolism not yet identified.

Summary The value of bromocriptine in the treatment of hirsutism in polycystic ovary syndrome (PCO) was assessed subjectively and photographically in a double-blind trial in 22 women studied for 1 year. Menstrual frequency was recorded. Circulating concentrations of oestradiol, oestrone, testosterone, androstenedione, and sex hormone binding globulin (SHBG) were determined before treatment and after 6 and 12 months therapy. On the same occasions gonadotrophin concentrations (mean of 24 samples) and their response to 100 μg LHRH were determined. No evidence was found to support a therapeutic role for bromocriptine in the treatment of hirsutism or menstrual regulation in PCO. No biochemical changes were seen specific to bromocriptine therapy.

We selected a group of male dialysis patients complaining of sexual dysfunction in whom penile vascular insufficiency and drug-induced impotence had been excluded. Monitoring of nocturnal penile tumescence was used to confirm organic disturbance. Patients with normal serum prolactin concentrations (n = 18) had significantly lower serum zinc values than normal controls (P less than 0.001) and were entered in a 6-month double-blind study comparing oral zinc acetate with placebo. Patients with elevated prolactin concentrations (n = 8) were entered in a 3-month double-blind crossover study comparing oral pergolide mesylate with placebo. In the zinc study, serum zinc concentrations increased (P less than 0.05) in the zinc-treated but not the placebo-treated group. One of nine patients receiving zinc reported improved sexual function, as did two of nine patients receiving placebo. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations in either treatment group. In the pergolide study, serum prolactin values decreased (P less than 0.01) in the pergolide but not in the placebo treatment period. One patient reported improved sexual function during the pergolide treatment period and two during the placebo period. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations after pergolide. These studies show no benefit of zinc or pergolide compared with placebo in the treatment of uraemic impotence.

The effect of zinc therapy and placebo on sexual function and endocrine status was investigated in a double-blind study of 14 male patients with chronic renal failure on regular haemodialysis. Zinc chloride was added to the dialysate of 7 patients for 6 weeks, raising the serum zinc concentration by 17% and placebo was added to the dialysate of the other patients. At the start of the trial 9 patients said they had decreased sexual function. Records of penile erectile activity during sleep confirmed the organic nature of the sexual dysfunction. Plasma testosterone concentrations were low or in the low normal range, basal serum luteinising-hormone levels were raised, and the early luteinising-hormone response to luteinising-hormone-releasing hormone was exaggerated, suggesting primary testicular failure. Zinc administration had no significant effect on any aspect of sexual function assessed by questionnaire or nocturnal penile tumescence monitoring. Plasma testosterone and basal and stimulated gonadotrophin levels were also unaltered by zinc administration.

SUMMARY The effect of chronic administration of bromocriptine to 20 patients with the polycystic ovary syndrome (PCOS) was studied. All patients had normal serum prolactin levels. Bromocriptine 7-5 mg daily was administered for up to 1 year and the biochemical and clinical responses assessed at 3-monthly intervals. Over a period of 3 to 12 months significant reductions in serum LH levels, LH/FSH ratios and in plasma testosterone were observed. In 14 patients, blunting of the previously enhanced LH response to LHRH was observed. Clinical improvement also occurred, most notably in menstrual function. In 12 out of 20 patients a monthly cycle was established and in a further three there was an increase in the frequency of menstruation towards normal. Eleven out of 20 patients ultimately noted a subjective improvement in hirsutism. We conclude that bromocriptine, given to patients with polycystic ovarian disease, inhibits LH hypersecretion, leading to restoration of cyclic ovarian function and reduced androgen synthesis.

Sixty-six per cent of a group of 21 renal transplant recipients with chronic renal failure were shown to have adrenal suppression due to glucocorticoid treatment. Gradual withdrawal of steroids in these patients returning to maintenance dialysis therapy was achieved with few symptoms of hypoadrenalism. Adrenal recovery occurred in 52 per cent of patients after three months and 71 per cent after six months. However, the plasma cortisol response to insulininduced hypoglycaemia, studied in patients in whom adrenal recovery had been demonstrated, was impaired in 46 per cent of cases. These results indicate that corticosteroids in renal transplant recipients induce profound hypothalamic-pituitary-adrenal suppression which is slow to recover. Such patients returning to maintenance dialysis are at risk of acute adrenocortical insufficiency for several months. Although withdrawal of steroids can be achieved safely, cover during periods of stress should be given until the hypothalamic-pituitary-adrenal axis has been shown to respond normally.